A user-friendly tool for analysis of complex in vitro experimental data in drug discovery and development

体外-活体外推(IVE)是药物开发中一个迅速崛起的领域，通过分析在组织匀浆或细胞中产生的体外实验药代动力学/药效学(PK-PD)数据，并将结果合并到计算机模型中以预测整体药物的效果。全细胞系统中的PK-PD数据分析是复杂和耗时的，但准确的数据分析和知情的数据解释在早期药物开发中至关重要，因为这些信息被用来选择在人体试验中评估的药物。虽然有许多软件工具可用于体外数据分析，但这些工具是为广泛应用而开发的，并不是专门用于药物开发的。这些工具不支持对更复杂的体外实验系统的分析，这些系统正越来越多地被用于克服药物开发中的新挑战，缺乏适当的统计严谨性，并且不允许静脉注射。该项目将提供一个用户友好的软件工具，首先分析描述药物代谢、运输和受体结合的体外数据。由数据分析引起的实验不确定度也将被确定。从体外数据分析得出的结果和任何相关的不确定度都将被外推，以描述药物在全身的行为。该工具将使非专家用户能够确定产生的体外数据的质量，以及在决策过程中使用估计参数的适当性。该工具的开发和使用将使整个制药行业的数据分析保持一致。该工具的使用最终将提高效率，增加IVIVE和药物动力学/药效学理解在药物开发中的效用。反过来，更多地使用IVIVE将有助于减少和取代早期药物开发中的动物实验。

In vitro-in vivo extrapolation (IVIVE) is a rapidly emerging area in drug developmentwhereby in vitro experimental pharmacokinetic / pharmacodynamic (PK-PD) data, generatedin tissue homogenates or cells, are analysed and the results incorporated into computer modelsto predict the effects of drugs in the whole body.PK-PD data analysis in whole cell systems is complex and time consuming, yet accurate dataanalysis and informed data interpretation are crucial in early drug development as thisinformation is used to select drugs to be assessed in human trials. Whilst there are manysoftware tools available for in vitro data analysis, these tools were developed for broadapplication and are not specialised for drug development use. The tools do not supportanalysis of more complex in vitro experimental systems which are increasingly being used inan attempt to overcome newer challenges in drug development, lack appropriate statisticalrigour and do not allow IVIVE.The project will provide a user-friendly software tool to analyse in vitro data describing themetabolism, transport and receptor binding of drugs in the first instance. The experimentaluncertainty arising from the data analysis will also be determined. The results derived fromthe in vitro data analysis and any associated uncertainty will be extrapolated to describe thebehaviour of the drug within the whole body. The tool will enable non-expert users todetermine the quality of the generated in vitro data, and the appropriateness of using theestimated parameters in the decision making process.The development and utilisation of this tool will allow consistency in data analysis across thepharmaceutical industry. Use of the tool will ultimately lead to improved efficiency andincrease the utility of IVIVE and pharmacokinetic / pharmacodynamic understanding in drugdevelopment. In turn, increased use of IVIVE will contribute to reducing and replacing animalexperiments within early drug development.